Simulated identification of silent COVID-19 infections among children and estimated future infection rates with vaccination

Importance: A significant proportion of COVID-19 transmission occurs silently during the pre-symptomatic and asymptomatic stages of infection. Children, while being important drivers of silent transmission, are not included in COVID-19 vaccination campaigns given their exclusion from clinical trials thus far. Objective: To investigate the impact of a targeted approach to identifying silent infections among children as a proxy for their vaccination. Design: This study used an age-structured disease transmission model to simulate the synergistic impact of interventions in reducing attack rates over the course of one year. Setting: A synthetic population representative of the demographics of the United States (US). Participants: Six age groups of 0-4, 5-10, 11-18, 19-49, 50-64, 65+ years old, stratified for their population size based on US census data. Exposures: Vaccination of adults, self-isolation of all symptomatic cases within 24 hours of symptom onset, and detection of silent infections. Main Outcomes and Measures: Vaccination of adults was implemented to reach a 40% coverage over the course of one year with a vaccine efficacy of 95% against symptomatic and severe COVID-19. Without vaccination of children, we determined the proportion and speed that would be required for identifying silent infections among this age group to suppress future attack rates below 5%. Results: A targeted approach that identifies 20.6% and 28.6% of silent infections among children within 2 or 3 days post-infection, respectively, would be required to bring attack rates under 5% with vaccination of adults. If silent infections among children remained undetected, achieving the same attack rates would require an unrealistically high vaccination coverage (at least 82%) of this age group, in addition to the base-case 40% vaccination coverage of adults. The results were robust in sensitivity analyses with respect to vaccine efficacy against infection and reduced susceptibility of children to infection. Conclusions and Relevance: In the absence of vaccine availability for children, a targeted approach to rapid identification of silent COVID-19 infections in this age group can significantly mitigate disease burden. Without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.

[1]  V. Lee,et al.  Infectivity of asymptomatic versus symptomatic COVID-19 , 2020, The Lancet.

[2]  P. Dormitzer,et al.  Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine , 2020, The New England journal of medicine.

[3]  B. Singer,et al.  The impact of vaccination on COVID-19 outbreaks in the United States , 2020, medRxiv.

[4]  A. Galvani,et al.  Routine saliva testing for the identification of silent COVID-19 infections in healthcare workers , 2020, medRxiv.

[5]  Tara A. Whitten,et al.  Symptoms associated with a positive result for a swab for SARS-CoV-2 infection among children in Alberta , 2020, Canadian Medical Association Journal.

[6]  Philip Sutton,et al.  Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19 , 2020, Nature Communications.

[7]  Z. Hyde,et al.  COVID‐19, children and schools: overlooked and at risk , 2020, The Medical journal of Australia.

[8]  A. Galvani,et al.  The impact of mask-wearing and shelter-in-place on COVID-19 outbreaks in the United States , 2020, International Journal of Infectious Diseases.

[9]  R. Baric,et al.  Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults , 2020, The New England journal of medicine.

[10]  N. Kaminski,et al.  Reduced development of COVID-19 in children reveals molecular checkpoints gating pathogenesis illuminating potential therapeutics , 2020, Proceedings of the National Academy of Sciences.

[11]  Georgia Salanti,et al.  Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis , 2020, medRxiv.

[12]  R. DeBiasi,et al.  Symptomatic and Asymptomatic Viral Shedding in Pediatric Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Under the Surface. , 2020, JAMA pediatrics.

[13]  B. Singer,et al.  The implications of silent transmission for the control of COVID-19 outbreaks , 2020, Proceedings of the National Academy of Sciences.

[14]  S. Bhatt,et al.  Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe , 2020, Nature.

[15]  W. Xu,et al.  The role of children in transmission of SARS-CoV-2: A rapid review , 2020, Journal of global health.

[16]  W. Wei,et al.  Presymptomatic Transmission of SARS-CoV-2 — Singapore, January 23–March 16, 2020 , 2020, MMWR. Morbidity and mortality weekly report.

[17]  Quentin J. Leclerc,et al.  Quantifying the impact of physical distance measures on the transmission of COVID-19 in the UK , 2020, BMC Medicine.

[18]  N. G. Davies,et al.  Age-dependent effects in the transmission and control of COVID-19 epidemics , 2020, Nature Medicine.

[19]  Eric H. Y. Lau,et al.  Temporal dynamics in viral shedding and transmissibility of COVID-19 , 2020, Nature Medicine.

[20]  Agata Mikolajczyk,et al.  The positive impact of lockdown in Wuhan on containing the COVID-19 outbreak in China , 2020, Journal of travel medicine.

[21]  Ruiyun Li,et al.  Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2) , 2020, Science.

[22]  G. Chowell,et al.  Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020 , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[23]  N. Linton,et al.  Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19) , 2020, International Journal of Infectious Diseases.

[24]  Jing Zhao,et al.  Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia , 2020, The New England journal of medicine.

[25]  R. Mikolajczyk,et al.  Social Contacts and Mixing Patterns Relevant to the Spread of Infectious Diseases , 2008, PLoS medicine.

[26]  R. Basmaci,et al.  Systematic Severe Acute Respiratory Syndrome Coronavirus 2 Screening at Hospital Admission in Children: A French Prospective Multicenter Study , 2021 .

[27]  The use of saliva as an alternate specimen for SARS-CoV-2 (COVID-19) PCR testing , 2020 .

[28]  J. Heesterbeek,et al.  On the Definition and the Computation of the Basic Reproduction Ratio , 2009 .

[29]  O. Diekmann,et al.  On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases in heterogeneous populations , 1990, Journal of mathematical biology.